Most studies of human immunity to Pseudomonas aeruginosa have focused on strains with typical morphology rather than the mucoid strains (MPA) prevalent in the respiratory tracts of patients with cystic fibrosis. Colonization with these strains is common in CF and the presence of MPA is associated with more advanced pulmonary disease and poorer prognosis. Antibiotic treatment will not eradicate these strains. Therefore, primary prevention is the most likely means of control. The few studies of immunity to MPA have utilized tests of primary antigen-antibody association rather than functional tests such as in vitro opsonization. Using an opsonic assay I have shown that the antigenic determinant primarily responsible for opsonic specificty of non-mucoid strains, immunotype antigen which is primarily lipopolysaccharide, may not be relevant for MPA. MPA appear to be resistant to opsonization by antibody to this antigen. Studies are currently underway to determine whether patients with cystic fibrosis have opsonic antibody to their MPA isolates and preliminary results from studies to patients' sera suggest that there is not uniformity, but some definitely have activity. I plan to study additional patients with CF to determine whether they have opsonic antibody toward their isolates and whether is it functionally specific for the mucoid or non-mucoid morphologic variants. Additional studies involve the study of MPA for complement receptors and further differentiation of the complement pathway(s) utilized by strains requiring complement alone or complement and antibody for opsonization. Studies of the immunogenicity of MPA in rabbits are proposed to look at the functional immunospecificity of the mucoid strain-specific antigen. By developing an assay to measure specific antibody to the exopolysaccharide of MPA it will be possible to determine the importance of this material as an antigen in the rabbits immune response and then in the sera of patients with CF. These studies will be the earliest steps for the evaluation of this material as a possible immunogen for eventual vaccination of patients with cystic fibrosis to prevent infection with MPA.